title: Frequent detection of mutations in the 5' flanking region of the prostate-specific antigen gene in female breast cancer.
abstract: Prostate-specific antigen (PSA) is expressed in normal, hyperplastic and cancerous female breast tissue. Expression is regulated by steroid hormones. Some breast tumours produce very high levels of PSA, while other do not express any PSA. In this study, we selected three primary breast tumours which overexpressed PSA (PSA protein concentration in tumour cytosols > 4300 ng/l) and three tumours which were negative for PSA (< 1 ng/l). We extracted DNA and sequenced all five exons of the PSA gene. No mutations were found in the PSA coding sequence in any of the tumours. We identified only two polymorphic sites in exon 2. We also sequenced parts of the 5' flanking region of the PSA gene in five tumours. All tumour DNAs contained abnormalities which consisted of point mutations and deletions of 1-7 base pairs. Except for one tumour which had only a 3 base pair deletion, all other tumours had multiple abnormalities (up to seven in one tumour). The deletions occurred adjacent to direct repeats similarly to deletions seen in the p53 gene. Our data suggest that the coding sequence of PSA is not mutated in breast cancer. However, the 1.4 kb 5'-flanking region was mutated in all five tumours tested. The importance of this observation in relation to PSA gene regulation and breast cancer pathobiology remain to be determined.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Tsuyuki
authors.forename: L
authors.initials: L
authors.lastname: Grass
authors.forename: E P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D017421:Sequence Analysis
chemical_list: D017430:Prostate-Specific Antigen